1,2,4-Thiadiazole is a distinctive class of small heterocyclic thiol trapping agents that serve as an interesting pharmacophore in the design of inhibitors targeting the cysteine residues of proteins. X-Ray crystal structures of enzyme-inhibitor complex indicate that the cysteine thiol reacts with the N-S bond of the thiadiazole moiety to form a disulfide bond resulting in the inactivation of the enzymes. This presentation addresses the medicinal chemistry and various properties of 1,2,4-thiadiazoles in their potential as new electrophilic “warheads” for targeting the cysteine residues of biomolecules (e.g, H+/K+ ATPase), and cysteine-dependent enzymes (e.g., cathepsin B and transglutaminase).
Keywords: Thiadiazole, proton pump, cathepsin B, Factor XIIIa, transglutaminase, cysteine thiol, inhibitors
Back to Proteinase
Back to The 37th Middle Atlantic Regional Meeting (May 22-25, 2005)